Application of cellulose derivatives



Patented Apr. 1, 1941 APPLICATION OF cELLULosr-i DERIVATIVES VincentJerome Flynn, Brooklyn, N. Y., assignor to Wardlyn Corporation, UnionCity, IN. 1., a

corporation oi New Jersey No Drawing. Application September 29, 1938,

Serial-No. 232,408

7 Claims. (01.128-349) This invention relates to compositions of tubesof varying size, shape and length partially or wholly composed oforganic derivatives of cellulose, or pieces of cellulose derivatives,either solid or hollow, or circular, oval, elliptical, square,rectangular or of other cross-sectional shape, and in general,- tosurgical devices comprehended under the terms exploratory andevacuative, as catheters, sounds or cannulae, being when solid, in-

tended for distending a passage, and when hollow for insertion into anormal opening of the body for injection or withdrawal of fluids thereinor therefrom and for medicamentation, or. for insertion into an incisionas in post-operative work, for drainage and other purposes.

By the term "catheter as herein applied, is to be understood ascomprehending the various sizes, shapes and lengths of (usually) hollowconwith the desired flexibility to penetrate body canals, especially theureter where the canal diameter is relatively small and more or lesstortuous, and which may be constricted or even substantially closed bymeans of abnormal or other.

conditions present therein.

The "hard rubber catheters while they may be of the desired rigidity,are deficient in suppleness and pliabllity. The comparatively largeamounts of sulfur and sulfur compounds contained therein, together withthe vulcanization accelerators, many of which are nitrogen compounds ofpronounced toxicity, materially militate against their struction forintroduction of a substance into the body through an opening or thewithdrawal .of fluids therefrom, and referred to under terms such asantrum, colonic, elbowed, double-elbowed, curved, eustachian, faucial,female, in-dwelling, prostatic, or winged catheters, tubes, irrigators,and by other names.

effectiveness and narrow their range of safe applicability, Furthermore,hard rubber catheters are prone to injure and wound delicate membraneswhich are often extremely tender and susceptible due to irritations andinflammatory conditions so that the use. of these cathetersis materiallylimited, both as to scope of application and to the technique andexperience of the manipulator. Catheters are often used by the layman,sometimes daily, as in prostatic enlargement Heretofore, catheters havebeen made of various materials showing a degree of flexibility, such as,thin metal tubing, rubber of varying stages of vulcanization, andcompounds in the liquid or semi-liquid condition built up over a web asof a fabric, usually b repeated dipping of the same in a solution of thecoating or impregnating material.

Metal catheters are harsh to delicate membranes, prone to irritateandwound tissues upon insertion, especially when the tissues are ultrasensitive and unusually delicate, as in inflammatory and certainpathological processes and normal and pathologic secretions exert asolvent effect on the metal which with some metals is very marked. Theircomparatively low elasticity is also a disadvantage to their extensiveapplication, especially in urologicalwork such as urethral, ureteral andrenal exploration and in connection with the removal of some forms ofrenal calculi.

Catheters made of rubber vary greatly in elasticity and supplenessdependent upon the degree of vulcanization to which therubber has beensubjected. The soft rubber catheters are highly elastic, but more orless porous and spongy, causing difiiculty in sterilization andrequiring such rigid sterilization treatments as to materially shortentheir period of effectiveness. The also, in general, lack the requisiterigidity coupled and analogous complications, and the unyieldingproperty of vulcanized-rubber often initiates irritation, which, whencontinued, may and does lead to serious chronic results.

Glass catheters, while usually of smooth surface, have a very lowelasticity and suppleness,

and there is always present the grave danger of breakage or chippingoff, especially where the glass wall is of relatively extreme thinness,as is sometimes the case. For this andother reasons, the use of glasscatheters involves an element of danger, and in addition they have alimited and decreasing range of applicability.

Enamel catheters, that is, catheters made of glazed porcelain, are usedto a limited extent. They are practically rigid with zero flexibility,of relatively rough interior due to the difliculties of interiorglazing, and very fragile in the thin cell wall diameter as usuallyprepared. By virtue of this inherent rigidity enamel catheters areuseless for adaptation to the varying contour of the canal into whichthey are intended to be inserted, and the rough interior introduces thedanger of incomplete sterilization.

One of the objects of my invention is to overcome and minimize theherein enumerated and other disadvantages, while still conserving thepoints of desirability of these instruments as a class, as applied tothe various uses for which they are normally intended, and I have foundthat most of the inherent objections are overcome where the cathetermaterial is composed of an etherized cellulose, especially where. thedegree of etherlfication approaches the maximum.

By etherized cellulose as herein used, is to be understood commerciallyalkylated, arylated or of cellulose ethers, and where additionalsuppleness, elasticity, etc., is desired, suitableplastiaralkylated, bymeans of a harmonious solvent,

solvent mixture, plastifler or thermoplasticizlng composition, the wholeafterwards being colloided by known means into a homogeneously appearingwhole. Asuitable example for use in the catheter art is a mixture ofhighly ethylated cellulose with either a highly benzylated cellulose ora highly cizers, flexilizers, softeners,( extensiflers orsuppleness-inducing componentsmay be incorporated with the celluloseether in an -amount and of a nature to impart thekind and degree of'characteristics desired. 'The highly etherified ethyl-celluloses andbenzyl-celluloses have been found especially useful in this connection;on account of the number and amount of suitable plastifying componentswhichmay be harmoniously incorporated therewith to induce the spec 0properties required and the extent of the same desired.

The cellulose ethers, as a class, are insoluble in, and notdetrimentally affected by ptyalin, pepsin, trypsin, oleopsin, steapsin,and other body enzymes and fluids, the products elaborated in the gallbladder, liver and kidney, both those that are normal to the healthybody and'those formed under pathological conditions: they can beproduced of a high degree, of flexibility, and are not adverselyaffected by the usual antiseptics, disinfectants, bactericides, boththose of metallic and non-metallic origin, usually applied forsterilization purposes.

As is well known, many of the normal or pathological body secretionseither are distinctly acid in reaction as the hydrochloric acid in thegastric juice} the bile acids, uric acid and the like, while othersecretions are of pronounced alkaline reaction. These chemicallyreactive bodies often aided by enzymic action, exert an appreciabledissolving and decomposing effect upon a catheter or instrument ofanalogous use, when made of rubber or a cellulose ester, especiallywhere in some instances, the tubular surgical device is left in the bodyfor an extended'period as often is the case in drainage treatments. Withthe simple cellulose esters, as the nitrate or the acetate, a v

saponifying action results, whereby a decomposition of the celluloseester takes place by a splitting off of acid radical.

As the culmination of a series of quantitative researches, thesurprising and unobvious observation has been made, that physicalmixtures of dissimilar cellulose ethers, and specifically suchetherified celluloses of comparatively high degree of etherification,are substantially insoluble in and unaffected by chemical and othercomponents elaborated by or in the humanbody in health and disease.

This has been found to hold true to the maximum degree when the physicalmixture of cellulose ethers contains ethylcellulose as one of thecellulose ethers employed, and where the ethylation of the cellulose hasbeen allowed to proceed to commercially the maximum, that is to say,where ethylation of the cellulose has resulted in theintroduction ofethyl or ethoxy rests to the propylated or ,butylated cellulose, aswithin the ratio of one part of one to three parts of the other. t

The word maximum as herein usedin connection with the etheriflcation ofcellulose or other carbohydrate, varies considerably in com mercialprocesses, depending upon the nature of the etherlfying process andthe'efilciencyof the .particular apparatus employed in the variousetherifying steps.

alloys, a similar phenomenon is known wherein i the alloy melts lowerthan any of the constituents therein.

This invention does not include the methycellu'loses, or thoseetherified celluloses which are appreciably affected by water, and islimited to etherified celluloses of substantially maximum degree ofetheriflcation.

My solubility experiments have also shown that the tendency to swell bythe action of water is lessened when twohighly etherified celluloses arephysically admixed, over that found by the cellulose ethers individuallyand separately. On account of their entire indifference tosaponiflcation, emulsification and other deteriorating infiuences, theetherized celluloses, especially when of a high degree ofetheriflcation, combine high stability, neutrality, and aresubstantially insoluble in or unaffected by the body fluids both normaland pathological.

The cellulose ethers as a body are characterized by relatively greatstability and apathy to reaction with chemical reagents, while stillconserving an unusually high degree of inherent flexibility, Thecellulose ethers may be treated with lye solutions of high concentrationwith impunity, since there is no acid radical to saponify off byalkaline treatment as is the case with the cellulose esters, and inaddition they are inert to many chemicals which injuriously affectrubber and other materials of which catheters of the present art aremade. to increase the elasticity of rubber at will by the addition ofproducts thereto, whereas with It is impossible the cellulose ethers, byselection of the appro-;

adapts the celluloseethers for use in the catheter industry. Phenols,iodides and other halogen inorganic or organic compound of normalbacaction to the cellulose ethers of degree of etheriflcationcomprehended herein.

I tericidal concentration are inert in unfavorable The antiseptic, localanesthetic, fungicide,

bactericide, medicament, or other addition of therapeutic value to thecatheter substance may be incorporated therewith in any approved manner, such, for instance, as dissolving the same in a relatively smallamount of harmonious solvent or solvent combination, incorporatingmentally affecting their normal stability or usefulness; and theelasticity, being inherent in the cellulose ether body, persistsunchanged for an indefinite period of time. Therefore, a widely, varyingdegree of desirable properties may be obtained, especially as toelasticity, plasticity, suppleness and flexibility of the ether, andthese inherent desirable properties may be consider-' ably enhanced bythe addition to the cellulose ethers of suitable plasticizing bodies nowknown to the cellulose ether art, such as aliphatic and carbocyclicesters of lactic, glycollic,tartaric, phthalicancl other acidsr arylphosphates, ,cyclohexanol esters, synthetic resinous bodies such as thehalogenated diphenyls, the substituted sulfonamides, and the like.

A catheter, in general, may be considered as a tube, straight, curved,elbowed, etc.,.depen ding upon the usefor which it is normally intended,and usually comprises an outer end or end held by the operator, whichmay be of the same exterior diameter as the remainder of the,tube

- nature required for the specific purpose intended.

portion or may be flared or otherwise enlarged; 1

the opposite end called the tip or beak, being that end intended forinsertion, and which may be of the same diameter as the tube portion, ormay be smaller, and is usually made in many shapes and in a variety ofways. The tip may be a portion of the original tube with one or moreorifices therein, or itmay be a separate piece immovably attached to thebody of the catheter tube by means of an agglutinant, by fusion; or inany other manner. configuration, length, and number of orifices therein,may vary considerably, depending upon the specific use to which theinstrumentis to be applied.

Having determined the degree of ether properties intended from thedesired use for which the instrument is designed, the kind, nature andproportion of dissimilar cellulose ethers is selected, the amount andkind of thermoplasticizing body added if any be used, and thecomposition by means of solvents, non-solvents and solvent andnon-solvent combinations, gelatinized, homogenized, plasticized orcolloided to the degree required, then extruded through an orifice ofappropriate size and shape, into tubular or other form.

In general, it has been found the melting point is raised and thedeleterious action of water on The shape,

the cellulose ether decreases with the number of similar or dissimilarradicals in the etherized cellulose. For the above and other reasons, Ihave obtained most satisfactory results herein by employing a physicalmixture of cellulose ethers approaching substantially as nearly ascommercially feasible, the maximum in etherification.

The exterior surface of thematerial may be modified as by smoothing,dipping in a cellulose ester, cellulose ether, or other lacquer orcoating composition, to increase the hardness, lessen the degree ofpermeability or for other reasons, after which the tube portion isexpanded or the diameter otherwise modified at the outer end, and thetip or beak portion may be punched, drilled, or otherwise one or moreorifices placed therein after closing the beak end, as with a celluloseether compositiomor a separate tip may be made and coapted onto the tubeportion by means of an adhesive, by heat, by heat and pressure, or inany other way, said tip being of the size and The number, size, spacingand location of orifices in the beak portion may be modified at will.

The cellulose ether composition may be colored, with dye or pigment orboth, to render the instrument distinctive upon observation: it may beprinted or lithographed upon, either under or on the final exterior coatif the extruded member is subjected to a dipping process afterextrusion, or various antiseptics, remedial agents,

analgesics or local anesthetics may be incorporated in the celluloseether plastic mass to induce a therapeutic eifect on the organs witlrwhich the catheter may normally be brought into contact. Urethral andespecially ureteral catheter explorations are usually relatively painfuloperations;- so that the incorporation within the catheter mass of localanesthetics, analgesics and the like, is often indicated.

Before extrusion-into tubular form, and especially where the instrumentis intended primarily for urological work aswith urethral and ureteralcatheters, the cellulose ether may have incorporated therewith andtherein, varying proportions of opacity inducing bodies of value inX-ray work, .such as bismuth salts (the normal nitrate or subnitrate),lead sulfates and lead salts, barium salts such as barium sulfate orbarium titanate and other salts or mixtures of salts suit able for thispurpose, As an example, given for illustrative purposes only, I havefound an excellent composition for this purpose to be com-- posed ofparts cellulose ether plastic mass to about 100 to parts lead sulfate,although these proportions may be varied, from the amounts above stated,depending upon the cellulose ether composition, the dimensions andthickness of the catheter tube, the nature of the opacityinducing bodyused, and the particular roentgenological diagnosis to be made.

Urethral catheters are usually flared on the outer end, substantiallyround, of exterior diameter 0.06 to 0.25 inch, interior diametersufflciently large usually to admit a ureteral catheten' v Ureteralcatheters are usually not flared on the junta end, and vary in tubediameter from 0.04

to 0.10 inch external and about 0.015 inch internal diameters. Forcolonic work, a round the is usually used, the exterior diameter beingup to 0.75 inch diameter. An antrum catheter usually has an exteriordiameter range of 0.075 to 0.15 inch and a varying internal diameter.The exterior and interior diameters will, of course, be adjusted by theextrusion operation, taking into the consideration the amount, if any,

. substance.

of volatile solvent present and the relative Velatility'oi' theplasticizing portionadded to the cellulose ether prior to theextrusionoperation. The shape of the catheter tip may vary considerably,as in the olive, round or whistle tips. as examples.

In general, the substantially maximumethylated celluloses have arelatively high inherent thermoplasticity, which property may beconsiderably augmented and varied in degree by the incorporationtherewith, of suitable known cellulose ether plasticizers andflexibility-inducing compounds, and still conserve the relatively highand permanent stability to, and insolubility in, chemical reagents whichcharacterize the cellulose ethers-in general.

Likewise, it has beenfound that by the use 'of certain cellulose etherplasticizing and -thermoplasticizing agents, the stability of theetherized cellulose maybe augmented, the porosity diminished, and thesuppleness and flexibility materially increased, without concomitantlydecreasing otherwise valuable inherent characteristics.

There has been described a method of producing a catheter by firstforming a textile core, dipping the core into a'solution of cellulose orother compound, drying the same, then repeating the process until therehas been built up on the textile center or core a suflicient thicknessof layers for the purposes intended. However, such constructed tubes areporous," they have pinholes and blisterstherein which increase thenatural porosity, as compared with the cellulose ether composition ofthe naturefas herein set forth which has been compacted by thenecessarily high pressure involved in the extrusion operation to aunitary non-porous whole, and is composed of a unitary materialthroughout its With a fabric core catheter built up in manner as aboveindicated, there is tendency upon use for the textile core to becomefrayed. and a fragment may be broken oil and remain in the bladder orkidney, thus providing a nucleus 'or nidus around which a calculus mayform. e I

Therefore,, the catheter involved in this invention is of homogeneousstructure throughout, and there is no dissimilar material core which maybreak. off, fray or cause an impediment in X-ray work or similarinvestigation, on account of variation of opacity.

At the close of. the extrusion operation, the catheter may be dipped,sprayed, or otherwise coated with a cellulose compound in solution,

and the instrument may be smoothed, polished, printed upon or otherwisetreated to produce a finished appearing instrument. The printingoperation may be conducted upon the extruded cellulose compound, eitherbefore or after the catheter is coated witha fluid compound, and eitherbefore or after the polishing or other finishing operation.

What I claim is:

l. A tubular surgical device comprising a physical mixture or a neutral,water-insoluble dissimilar etherized cellulose of maximum degree ofetherification.

2. A tubular surgical device comprising a water-insoluble alkylatedcellulose of maximum alkylation, admixed with adissimilar waterinsolubleetherifled cellulose of commercially maximumtetherification andcolloided.

3. A tubular surgical device comprising an alkylated cellulose ofmaximum alkylation, admixed with a dissimilar etherified cellulose ofmaximum alkylation, which has been colloided and extruded.

4. A tubular surgical device comprising a water-insoluble ethylatedcellulose of maximum ethylation homogeneously colloided with adissimilar water-insoluble etherified cellulose of maximumetheriflcation.

5. A flexible, tubular surgical device 0! homogeneous structure, saiddevice comprising a physical mixture of water-insoluble dissimilarthermoplasticized etherifled cellulose of maximum commercialetheriflcation.

6. A catheter comprising a colloided mixture of water-insolublecellulose ethers of dissimilar radicals, in which the combined degree ofetheriflcation of the cellulose is not less than oi that theoreticallypossible.

7. A catheter comprising a relatively long. hollow tube of smallexternal diameter formed by extrusion from a physical mixture of aneusubstantially inert to bodily fluids and medicaments and to have theother inherent characteristics aforesaid.

VINCENT JEROME FLYNN.

